Safety, pharmacokinetics, and pharmacodynamics of human interferon-α2b spray in healthy participants.

Abstract

The safety, pharmacokinetics (PK), and pharmacodynamics (PD) of multiple doses of human interferon (IFN)-α2b spray administered via nasal and oropharyngeal routes were evaluated in a randomized, double-blind, placebo-controlled study. Forty-eight healthy Chinese participants were randomized into three dose groups: low (450,000 IU/dose), medium (600,000 IU/dose), and high (750,000 IU/dose). In each group, 12 participants received the corresponding dose of IFN-α2b spray, and four participants received the placebo. All participants received a single nasal and oropharyngeal dose at 0 and 48 h, respectively, with the high-dose group receiving an additional topical abdominal skin dose at 96 h to assess skin irritation. Adverse events were observed and recorded throughout the trial. Plasma, nasal lavage fluid, and oral gargle samples were collected, with IFN concentration and interferon-inducible protein-10 level being determined as PK and PD indicators, respectively. The results suggest that IFN-α2b spray was safe and well-tolerated across all doses (450,000-750,000 IU) with no systemic exposure detected. PK/PD analysis showed a correlation between the PD index and the level of IFN exposure in nasal lavage fluid, while no significant correlation was observed in oral gargle samples. The IFN concentrations in all dose groups were higher than the half-maximal effective dose (ED₅₀), suggesting that the high dose could be considered for subsequent clinical trials.